Immediate Time Course of Drug Effect

Question 1

What do pharamcodynamics and pharmacokinetics describe?

Answer 1

The time course of a drug

Question 2

What specifically in the time course of a drug does pharmacokinetics and pharmacokinetics describe?

Answer 2

Pharmacokinetics describes the change in concentration of drug over time

Pharamcodynamics describe the change in effect over time as concentration changes.

Question 3

What are the three ways to think of the time course of a drug?

Answer 3

1) Drug effects are immediately related to observed drug concentration (plasma con.)
2) Drug effects are delayed in relation to observed drug concentration
3) Drug effects are determined by the cumulative action of the drug

Question 4

What are the two parameters of pharmacokinetics relevant to time course of a drug?

Answer 4

CL = Clearance
V = Volume of distribution

Question 5

What are the two parameters of pharmacodynamics relevant to time course of a drug?

Answer 5

Emax

C50 (EC50)

Question 6

What do pharmacokinetics and pharmacodynamics determine?

Answer 6

Dose
Concentration
Effect

Question 7

What is half life?

Answer 7

The time it takes for the concentration of drug to halve.

Question 8

What is Emax?

Answer 8

The affect of a drug at infinite concentration, cannot be truly known

Question 9

What does T0.5 and effect correlate?

Answer 9

When the concentration halves, the effect does not. It depends on the substance i.e may be 4 half lives before effect has halved.

Question 10

What is the relationship between effect and concentration?

Answer 10

Non-linear.

Hyperbolic curve as the binding to receptor and concentration follows this, therefore EC50 = kd

Question 11

Does the hyperbolic concentration effect curve ever reach 100%?

Answer 11

No it comes close but does not

Question 12

What does the log transformation to the hyperbolic curve do?

Answer 12

transforms it into a sigmoidal curve.

Question 13

What law dictates that the concentration response curve should be hyperbolic?

Answer 13

The law of mass action principal

Question 14

What part of the sigmoidal log concentration curve is near linear?

Answer 14

between 20-80% Emax

Question 15

What does the log concentration curve not account for?

Answer 15

That 0 concentration will have no effect, this is because log 0 is undefined

That there is a biological max, this is because mathematically emax can only occur at infinity concentration

Question 16

What is the Emax model?

Answer 16

Fundamental description of the concentration effect relationship

Question 17

Write the Emax model

Answer 17

E = (Emax. Conc) / (C50 + Conc)

Question 18

Define each parameter of the Emax model:

Answer 18

E = drug effect
Conc = Concentration at the receptor
Emax = max effect
C50 = concentration of drug at 50% receptor occupancy

Question 19

What are two other concentration values that are important other than C50?

Answer 19

C20 (1.4 C50)

C80 (4 times the C50)

This means from c20 to c50 this model predicts a 16 fold increase in concentration

Question 20

Define the sigmoid Emax model:

Answer 20

E = (Emax. Conc-Hill co efficient) / (C50-Hill co efficient + Conc-Hill co efficient)

Question 21

What is the Hill coefficient?

Answer 21

Determines the steepness of the graph, This accounts for co-operative binding in haemoglobin, as this changes depending on the amount of sites occupied.

Question 22

Using theophylloine as an example, describe its C50 on the concentration response curve:

Answer 22

C50 is obtained at around 10mg/L

While Emax is at 100mg/L

Question 23

What does the immediate effect of a drug depend on?

Answer 23

The initial concentration of the drug and its pharmacodynamic properties.

Question 24

When the dose of drug give/ immediately following administration is C50, then what is observed regarding concentration time and effect time curves?

Answer 24

Time course of effect is almost parallel with time course of concentration.

Question 25

When the dose of drug give/ immediately following administration is 10x C50, then what is observed regarding concentration time and effect time curves?

Answer 25

Time course of concentration is always normal because the half life is constant and unchanged.

However the time course effect is greatly elevated (as the concentration is far higher than time course concentration curve) Review page 194

Question 26

When the dose of drug give/ immediately following administration is 100x C50, then what is observed regarding concentration time and effect time curves?

Answer 26

Time course of concentration is always normal because the half life is constant and unchanged.

However the time course effect is greatly elevated (as the concentration is far higher than time course concentration curve)

It takes a lot of half lives to reduce the effect being produced.

Question 27

How can the time course effect graph be divided?

Answer 27

Into three regions

Question 28

What are the three regions of the time course effect?

Answer 28

(Flat) C80< Then the curve us almost flat (no change), little change in effect despite big changes in concentration

(Linear) C20

Question 29

What does the duration of a response rely on?

Answer 29

The amount of drug and its half life

i.e if the concentration of drug is doubled then the duration will increase by ONE half life

Question 30

Whats the most important clinical application of the Emax model?

Answer 30

The prediction of target concentration to produce target effect

Question 31

Whats the equation for determining the target concentration for target effect?

Answer 31

Conc = (C50 x Effect) / (Emax - Effect)

Question 32

What else is the emax model appropriate for?

Answer 32

Determining the dosing interval of a drug.

Takes into account target concentration, C50 and half life.

examples include

beta blockers
ACE inhibitors
Prednisone

Question 33

Can effect have a half life?

Answer 33

No not really, only during the exponential phase if at all